Biofilm in group A streptococcal necrotizing soft tissue infections

Siemens, Nikolai; Chakrakodi, Bhavya; Shambat, Srikanth Mairpady; Morgan, Marina S.; Bergsten, Helena; Hyldegaard, Ole; Skrede, Steinar; Arnell, Per; Madsen, Martin Bruun; Johansson, Linda; Juarez, Julius; Bošnjak, Lidija; Mörgelin, Matthias; Svensson, Mattias; Norrby‐Teglund, Anna

doi:10.1172/jci.insight.87882

Cited by 66 publications

(104 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, scanning electron microscopy (SEM) revealed that GAS biofilms on MEFs appear in chains within thick and multi-layered aggregates ( Fig. 2B), similar to previous reports of GAS biofilms in vivo (8,12). While JS95 is capable of forming biofilm on polystyrene tissue culture plates (referred hereafter as plastic), biofilms on this abiotic substratum accumulate less biomass compared to biofilms on MEFs, display different developmental kinetics, and have a 3-D architecture distinct from MEF-associated biofilms ( Figs.…”

Section: Gas Forms Biofilms On Mammalian Cellssupporting

confidence: 88%

“…Antibiotic treatment failure against susceptible clinical GAS isolates has been attributed to biofilm formation, given the increased tolerance of biofilm bacteria to antibiotics (9,10). Indeed, dense clusters of GAS microcolonies have been observed within the soft tissue of NF patients (11) and GAS isolated from human necrotizing soft tissue infections (NSTIs) appeared as multi-layered fibrous biofilms that persisted despite prolonged antibiotic therapy (12). However, despite evidence of biofilm-like communities during GAS infection, most research on the contribution of biofilms to the pathogenesis of GAS disease has been performed in vitro, where infection-associated environments are not fully recapitulated (13).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Streptolysin-induced endoplasmic reticulum stress promotes group A streptococcalin vivobiofilm formation and necrotizing fasciitis

Vajjala

Biswas

Chong

et al. 2017

Preprint

View full text Add to dashboard Cite

Group A Streptococcus (GAS) is a human pathogen that causes infections ranging from mild to fulminant and life-threatening. Biofilms have been implicated in acute GAS soft-tissue infections such as necrotizing fasciitis (NF). However, most in vitro models used to study GAS biofilms have been designed to mimic chronic infections and insufficiently recapitulate in vivo conditions and the hostpathogen interactions that might influence biofilm formation. Here we establish and characterize an in vitro model of GAS biofilm development on mammalian cells that simulates microcolony formation observed in a murine model of human NF. We show that on mammalian cells, GAS forms dense aggregates that display hallmark biofilm characteristics including a three-dimensional architecture and enhanced tolerance to antibiotics. In contrast to abiotic-grown biofilms, host-associated biofilms require the expression of secreted GAS streptolysins O and S (SLO, SLS) resulting in the release of a host-associated biofilm promoting-factor(s). Supernatants from GAS-infected mammalian cells or from cells treated with endoplasmic reticulum (ER) stressors restore biofilm formation to an SLO and SLS null mutant that is otherwise attenuated in biofilm formation on cells, together suggesting a role for streptolysin-induced ER stress in this process. In an in vivo mouse model, the streptolysin-null mutant is attenuated in both microcolony formation and bacterial spread, but pre-treatment of softtissue with an ER-stressor restores the ability of the mutant to form wild type like microcolonies that disseminate throughout the soft tissue. Taken together, we have identified a new role of streptolysindriven ER stress in GAS biofilm formation and NF disease progression. Significance StatementAlthough it is well-accepted that bacterial biofilms are associated with many chronic infections, little is known about the mechanisms by which group A Streptococcus (GAS) biofilms contribute to acute soft tissue-invasive diseases like necrotizing fasciitis (NF). In this study, we establish a physiologically relevant in vitro model to study GAS biofilm formation on mammalian cells and validate our findings in a mouse model that mimics human NF. This study demonstrates a novel role of GAS streptolysin-mediated ER stress in the development and spread of GAS biofilms in acute softnot peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/183012 doi: bioRxiv preprint first posted online Aug. 31, 2017; 3 tissue infections. We also show that biofilm formation depends on the release of a host-associated factor that promotes microcolony formation and GAS dissemination in vivo.

show abstract

Section: Gas Forms Biofilms On Mammalian Cellssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Streptolysin-induced endoplasmic reticulum stress promotes group A streptococcalin vivobiofilm formation and necrotizing fasciitis

Vajjala

Biswas

Chong

et al. 2017

Preprint

View full text Add to dashboard Cite

show abstract

“…These are followed by resistance to immune responses, tissue destruction and systemic GAS infection (16). The observation of necrotizing fasciitis biopsy support the in vivo relevance of these results (15). However, questions remain regarding the events occurring during the first hours of infection of the tissues, particularly whenever GAS is in contact with stromal tissues such as the decidua.…”

mentioning

confidence: 87%

“…The current model describing the invasive infections early steps, supported by studies on an infection model of 3D organotypic human skin, suggests adhesion to host tissue, growth, invasion of the tissue within 24 h pi (15). These are followed by resistance to immune responses, tissue destruction and systemic GAS infection (16).…”

mentioning

confidence: 96%

Streptococcus pyogenes infects human endometrium by limiting its immune response

Weckel¹,

Guilbert²,

Lambert³

et al. 2019

Preprint

View full text Add to dashboard Cite

Group A Streptococcus (GAS), a Gram-positive human-specific pathogen yields 517,000 deaths annually worldwide, including 163,000 due to invasive infections and among them puerperal fever. GAS is their most feared etiologic agent. Puerperal fever still accounts for more than 75,000 maternal deaths annually and before the introduction of efficient prophylactic measures 10% childbirths were followed by the mother's death. Yet little is known regarding GAS invasive infection establishment or GAS efficiency in causing postpartum infection. To characterize its early steps, we set up coordinated analyses of ex vivo infection of the human decidua, the puerperal fever portal of entry. We analyzed GAS behavior and the immune response triggered. We demonstrate that GAS (i) benefits from tissue secreted products to multiply; (ii) invades the tissue and leads to the death of half the cells within two hours via SpeB protease and Streptolysin O activities, respectively; (iii) impairs the tissue immune response. Immune impairment occurs both at the RNA level, with the induction of only a restricted immediate innate immune response, and at the protein level, in a SLO-and SpeB-dependent manner. Our study indicates that GAS efficient decidua invasion and immune response restraint favor its propensity to develop rapid invasive infections in a gynecological-obstetrical context.

show abstract

“…This early study demonstrated major hallmarks of many biofilm infections: the presence of a foreign body, which promotes a persistent infection with a low level of inflammation that subsequently leads to tissue destruction. Such were hard to resolve necrotizing soft tissue infections caused by group A Streptococcus pyogenes , usually a rapidly progressing acute infection, recently observed to be associated with in situ biofilm formation, accompanied by a higher bacterial load and an elevated immune response [4]. …”

Section: Diagnosis Of Biofilm Infectionsmentioning

confidence: 99%

Biofilm formation – what we can learn from recent developments

et al. 2018

View full text Add to dashboard Cite

Although biofilms have been observed early in the history of microbial research, their impact has only recently been fully recognized. Biofilm infections, which contribute to up to 80% of human microbial infections, are associated with common human disorders, such as diabetes mellitus and poor dental hygiene, but also with medical implants. The associated chronic infections such as wound infections, dental caries and periodontitis significantly enhance morbidity, affect quality of life and can aid development of follow-up diseases such as cancer. Biofilm infections remain challenging to treat and antibiotic monotherapy is often insufficient, although some rediscovered traditional compounds have shown surprising efficiency. Innovative anti-biofilm strategies include application of anti-biofilm small molecules, intrinsic or external stimulation of production of reactive molecules, utilization of materials with antimicrobial properties and dispersion of biofilms by digestion of the extracellular matrix, also in combination with physical biofilm breakdown. Although basic principles of biofilm formation have been deciphered, the molecular understanding of the formation and structural organization of various types of biofilms has just begun to emerge. Basic studies of biofilm physiology have also resulted in an unexpected discovery of cyclic dinucleotide second messengers that are involved in interkingdom crosstalk via specific mammalian receptors. These findings even open up new venues for exploring novel anti-biofilm strategies.

show abstract

Biofilm in group A streptococcal necrotizing soft tissue infections

Cited by 66 publications

References 29 publications

Streptolysin-induced endoplasmic reticulum stress promotes group A streptococcalin vivobiofilm formation and necrotizing fasciitis

Streptolysin-induced endoplasmic reticulum stress promotes group A streptococcalin vivobiofilm formation and necrotizing fasciitis

Streptococcus pyogenes infects human endometrium by limiting its immune response

Biofilm formation – what we can learn from recent developments

Contact Info

Product

Resources

About